Radiation dose for Hodgkin's lymphoma may increase valvular heart disease risk
Patients who receive radiation to the heart valves during treatment for Hodgkin’s lymphoma may be at increased risk for clinically significant valvular heart disease, according to study results.
The risk appeared highest among those who received doses greater than 30 Gy, results showed.
Prior studies have documented that radiotherapy can cause cardiovascular mortality and morbidity in long-term survivors of Hodgkin’s lymphoma. Greater awareness of this risk — as well as increased use of combination treatment with chemotherapy and radiation — has contributed to reductions in radiotherapy doses and volumes, but radiation still can increase risk for heart disease if the targeted field is in the chest cavity, according to study background.
Berthe M. P. Aleman, MD, PhD, a radiation oncologist at the Netherlands Cancer Institute, and colleagues conducted case-control study to assess the dose-response relationship of radiation therapy and valvular heart disease, and to identify other possible factors that increase risk for valvular heart disease among patients with Hodgkin’s lymphoma who receive incidental irradiation of the heart.
The analysis included 1,852 patients treated at one of three Dutch institutions between 1965 and 1995. All patients were diagnosed with Hodgkin’s lymphoma between ages 15 and 41 years, and they all had survived at least 5 years after diagnosis.
Median follow-up was 18.8 years (interquartile range, 13.1-25.6).
Researchers identified 89 patients who developed valvular heart disease, 66 of which were characterized as severe or life-threatening. The aortic valves (n = 63) and mitral valves (n = 42) were the most frequently affected, according to researchers.
Aleman and colleagues paired each case patient with three controls matched for gender, as well as age at and date of Hodgkin’s lymphoma diagnosis.
At 30 years, the cumulative risk for valvular heart disease among the cohort was 8% (95% CI, 6.2-10). The median interval between diagnosis of Hodgkin’s lymphoma and diagnosis of valvular heart disease was 23.3 years.
Results showed risks for valvular heart disease increased with radiation dose. Risks increased by factors of 1.4 for doses of 30 Gy or less; 3.1 for doses of 31 Gy to 35 Gy; 5.4 for doses of 36 Gy to 40 Gy; and 11.8 for doses of more than 40 Gy (P < .001).
Overall, the cumulative risk for valvular heart disease at 30 years after Hodgkin’s lymphoma diagnosis was 8% (95% CI, 6.2-10). Risks were 3% among those who received radiation doses of 30 Gy or less; 6.4% among those who received doses of 31 Gy to 35 Gy; 9.3% among those who received doses of 36 Gy to 40 Gy; and 12.4% among those who received doses of more than 40 Gy.
If splenectomy was required, the rate of vascular heart disease rose by a factor of 2.3 (95% CI, 1.1-4.5).
The standard radiation dose for Hodgkin’s lymphoma is 20 Gy or 30 Gy. Therefore, researchers determined patients with mediastinal involvement who have heart valves exposed to those radiation doses would be 1.4% more likely to develop clinically significant vascular heart disease after 30 years than patients who did not receive radiation as part of Hodgkin’s lymphoma treatment.
“This confirms that radiation dose to the heart valves is the main risk factor for the development of clinically significant valvular heart disease following treatment for Hodgkin’s lymphoma,” Aleman and colleagues wrote. “It is the first time that a dose-response relationship has been derived in terms that can be easily translated into clinical practice. It will help clinicians assess the risk of vascular heart disease for patients treated in the future and will assist in guiding the appropriate follow-up of Hodgkin’s lymphoma survivors.” – by Anthony SanFilippo
Disclosure: The researchers report funding from the British Heart Foundation, the Cancer Research UK, the Dutch Cancer Society and the UK Medical Research Council.